微小RNA基因多态与乳腺癌易感性的关系

Polymorphisms of microRNA genes and their association with breast cancer risk

目的探讨微小RNA（miRNA）基因序列的单核苷酸多态（SNP）位点与乳腺癌患病风险之间的关系，以期分析可用于易感人群筛查的分子标志物。方法选取经病理证实的乳腺癌患者（病例组）384例，选取与病例组患者年龄匹配的正常健康对照（对照组）192例，均为汉族、女性，均经5年以上随诊证实无恶性肿瘤病史。根据美国国立生物技术信息中心和microRNA Base公共数据库信息，选择已知汉族人群中全部miRNA最小等位基因频率〉0．05的SNP位点，最终入选22条miRNA基因的23个位点。采用高通量的MassARRAY时间飞行质谱生物芯片系统分析候选位点的基因型。采用非条件Logistic回归模型评估候选位点与乳腺癌患病风险的关系。结果全组研究对象年龄21～81岁，中位年龄48岁。病例组患者的年龄分布、吸烟状态与对照组比较，差异均无统计学意义（均P〉0．05）。病例组和对照组伴有乳腺癌或卵巢癌家族史者所占比例分别为9．1％和1．6％，初潮年龄≤14岁所占比例分别为53．1％和37．5％，未绝经者所占比例分别为61．2％和50．0％，差异均有统计学意义（均P〈0．05）。病例组miRNA基因SNP位点各基因型的分布频率与对照组比较，差异无统计学意义（P〉0．05）。结论存在于miRNA基因序列的SNP与汉族、女性乳腺癌患病风险无明显相关性。

Objective To explore the relationship between the polymorphisms of microRNA genes and the risk of breast cancer, and to analyze molecular markers which can be used in screening of susceptible population. Methods All the individuals included in this case-control study were genetically independent ethnic HaM Chinese. The breast cancer patient group consisted of 384 women confirmed by histopathology, and the control group consisted of 192 healthy female individuals. We screened genetic variants in all miRNA genes according to the public database miRBase and NCBI database. A total of twentythree common single nucleotide polymorphisms in twenty-two miRNAs, which tagged the known common variants with minor allele frequency greater than 0.05 were genotyped. A MassARRAY MALDI-TOF system was used for genotyping the candidate SNPs by the method described in the Sequenom Genotyping Protocol. The frequencies of SNPs were compared between cancer cases and controls to identify the SNPs associated with breast cancer susceptibility. Logistic regression analysis was applied to analyze the differences in genotype or allele frequencies of individual SNPs in cancer cases and controls, and to evaluate the correlation between candidate loci and breast cancer risk. Results The median age of the total group including 384 breast cancer patients and 192 control subjects was 48 years（ range, 21-81 years）. There were no significant differences in age distribution （P= 0.695） and smoking status （P = 0.193） between the case group and the control group. However, the number of patients with a family history of breast cancer or ovarian cancer in the case group was significantly higher than that in the control group（9.1% vs. 1.6%, P〈0.001 ）. The number of the patients with menarche age below 14 years in the case group was significantly higher than that in the control group （53.1% vs.37.5%, P〈0.O01 ）. The number of premenopausal patients in the case group was significantly higher than that in the control group （ 61.2% vs. 50.0%, P = 0.007 ）. There was no significant association between breast cancer risk and the single nucleotide polymorphisms in miRNA genes （P〉0.05）. Conclusions The genetic polymorphism of miRNA is not obviously associated with breast cancer risk among Chinese women.